The long term objective of this research program is to determine the efficacy of selenium as a chemopreventive agent for mammary tumorigenesis. Extensive evidence has accumulated to support the role of selenium as a potent chemopreventive agent for a number of epithelial-derived tumors, including mammary cancer. Currently, a mechanistic understanding of selenium's chemopreventive action is lacking. The proposed experiments are focused on a potential mediator of selenium's action, a selenium labeled protein of 56 Kd. The function of this protein is unknown and a survey of nucleotide and amino acid sequences in various data banks suggests it is a novel protein. The proposed experiments have 3 specific aims.
Aim 1 proposes to examine the effects of over expression of this protein on cell growth and function using both mammary epithelial cell lines in vitro and their derivative in vivo counterparts. A second specific aim examines the extent and type of phosphorylation of the protein and the effect of selenium binding on specific phosphorylation of this protein. The third specific aim continues to pursue in vivo experiments on the interaction of selenium compounds, vitamin E and 56 Kd protein during prevention of mouse mammary tumorigenesis. At the end of this project period, it is anticipated that the role of the 56 Kd protein in selenium mediated inhibition of cell growth and tumorigenesis will be further clarified and the interactions of selenium, vitamin E and 56 Kd protein will be documented.
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